Advances in vertebrate appendage development and its evolutionary mechanism

Abstract

Vertebrates display a vast array of morphological adaptations to ecological niches. These involve multiple large-scale changes of the appendages, such as evolving limbs from fins, wings (birds, bats), and even the loss of appendages (caecilians, lizards, snakes) during the transition from water to land. Reversals also exist, such as whales evolving back to having fins. This tremendous diversity of appendages leads to development of vertebrate appendage being a model for understanding the evolution and development of appendage morphologies. The development of appendages from buds is conserved among vertebrate. Appendage growth depends on cell proliferation and specializations along proximal-distal (PD), anterior-posterior (AP) and dorsal-ventral (DV) axes. Cell proliferation in lateral plate mesoderm relates to the initiation of buds. The growth of ectodermal cells forms an apical ectodermal ridge along the bud and secreted fibroblast growth factors (Fgfs) control outgrowth of the bud. Gene expression in a specific time and region and levels of expression determines if a bud becomes a fin, wing or limb. Several genes and regulation signal pathways have evolved during transition of fins to alternative types of limbs. Fgfs, Wnts, Shh, RA and Bmps signaling regulate the genes Tbx5 , Tbx4 , Fgf8 , and Bmp and the Hox gene family, respectively, which are essential for appendage development and evolution. These genes associate with chondrocyte proliferation and differentiation. T-box , fgfs and wnts in lateral plate mesoderm are essential for lateral bud initiation, which relates to the transition of ancestral median fins to paired fins. The origin of appendages for the emergence onto land was depended on regions and levels of expression for such as Bmp4 , Hoxd13 and hand2 , which bmps and shh signals regulate, respectively. Hox13 is expressed on the distal margin of fins and limbs buds while the larger-scale region of expression in the limb bud constitutes the basis of the development of the PD axis in terrestrial vertebrates. Loss of Hand2 leads to the deficiency of hind-limbs in whales. High levels of expression of Bmps in the forelimb of bats lead the forelimb to be longer than the hind-one. Furthermore, not only signaling regulation, but also transcription factors, regions of genome regulation and some long non-coding RNAs (lncRNAs) play regulatory roles in gene expression during appendage development.